MOLECULAR INSIGHTS TOWARD UNDERSTANDING PATHOLOGIES SUCH AS CHRONIC PAIN OR AMYOTROPHIC LATERAL SCLEROSIS…
The mammalian spinal cord functions as a community of cell types to perform sensory processing, autonomic control, or motor functions. Conversely, dysfunction of these cells in spinal cord injuries or pathological conditions can lead to dysfunctions including chronic pain, sphincter disorders, and paralysis and in the worst-case death. Although biomedical research has made great progresse strides in understanding the cellular diversity of the spinal cord in animal models, direct characterization of human biology to uncover the specialized features of the basic function of spinal cell types is crucial to better understand human pathologies.
An international collaboration led by Dr Ariel Levine’s team from the NIH in the USA and several american, canadian and french teams from the CHRU of Montpellier (Departments of Neurosurgery/Organ transplant) and the IGF (team headed by Emmanuel Bourinet) presents a study to be published in the journal Neuron that is the first cellular taxonomy of the adult human spinal cord using RNA sequencing technology on isolated cell nuclei. This work was possible thanks to a technique developed at the Montpellier University Hospital for the surgical removal of spinal cord from organ donors as part of transplant procedures according to the Biomedicine Agency, a procedure unique in Europe. In concrete terms, the work describes the great diversity of cell types in the human spinal cord, including glial and neuronal cells, which are organized mainly according to their anatomical location. In order to demonstrate the potential of this resource for the understanding of human disease, particular emphasis is placed on the analysis of the transcriptome of spinal motor neurons that are subject to degeneration in amyotrophic lateral sclerosis (ALS) more commonly known as Charcot disease. The finding of the work is that, relative to all other spinal neurons, human motor neurons are defined by genes related to cell size, cytoskeletal structure and ALS, supporting a model of a specialized molecular repertoire of motor neurons that underlies their selective vulnerability to disease in humans. The publication is accompanied by an open access web resource for the public and the entire international medical and scientific community, in the hope that it will catalyze future discoveries on human spinal cord biology and disease.
